ArticleFrontiers in psychiatry2020
The Antidepressant Effect of Ketamine Is Dampened by Concomitant Benzodiazepine Medication.
Article in Frontiers in psychiatry, 2020. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 24 papers, 3 of them syntheses that pooled it.
What it found
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The abstract states no effect estimate the extractor could read, or names no intervention and outcome on the map, so this paper lights no cell and moves no belief. It is still indexed, cited and linked below.
The trial behind it
Trials whose registry record cites this paper, or whose number appears in the abstract. A trial that started after this paper was published is citing it as background, not reporting it.
Neither the registry nor the abstract names a trial number. If this is a trial report, that itself is worth knowing.
Who cites it
24 citing papers in PubMed, 3 syntheses or guidelines pooled it, 45 citations in OpenAlex.
- Pooled it
- International pooled patient-level meta-analysis of ketamine infusion for depression: In search of clinical moderators.Molecular psychiatry · 2022Pooled it
- Blood-based biomarkers of antidepressant response to ketamine and esketamine: A systematic review and meta-analysis.Molecular psychiatry · 2022Pooled it
- Effect of ketamine intervention on hemodynamic responses in patients with treatment-resistant depression.Scientific reports · 2026Article
- Innovative Approaches to Depression Therapy: The Antidepressant Efficacy and Mechanisms of General Anesthetics.Current neuropharmacology · 2026Review
- Sympathetic activation but not dissociation linked to ketamine's sustained antidepressant effect.Therapeutic advances in psychopharmacology · 2026Article
- Rapid Symptom Reduction Following Intramuscular Ketamine in Refractory Obsessive-Compulsive Disorder: A Case Report.Case reports in psychiatry · 2026Article
- Rapid-acting NMDA and GABAergic Modulators in Mood Disorders: From Synaptic Mechanisms to Clinical Practice.Clinical psychopharmacology and neuroscience : the official scientific journal of the Korean College of Neuropsychopharmacology · 2025Review
- Optimizing ketamine dosing strategies across diverse clinical applications: a comprehensive review.Annals of medicine and surgery (2012) · 2025Review
- High Baseline Plasma Anthranilic Acid Predicts Remission Upon Acute-Series Ketamine Infusion for Treatment-Resistant Depression.Biological psychiatry global open science · 2025Article
- Personalized use of ketamine and esketamine for treatment-resistant depression.Translational psychiatry · 2024Review
- New Perspective for Drug-Drug Interaction in Perioperative Period.Journal of clinical medicine · 2023Review
- Ketamine and serotonergic psychedelics: An update on the mechanisms and biosignatures underlying rapid-acting antidepressant treatment.Neuropharmacology · 2023Review
- Use of ketamine for treatment resistant depression: updated review of literature and practical applications to a community ketamine program in Edmonton, Alberta, Canada.Frontiers in psychiatry · 2023Article
- Evaluating the effects of S-ketamine on postoperative delirium in elderly patients following total hip or knee arthroplasty under intraspinal anesthesia: a single-center randomized, double-blind, placebo-controlled, pragmatic study protocol.Frontiers in aging neuroscience · 2023Article
- Key considerations for the use of ketamine and esketamine for the treatment of depression: focusing on administration, safety, and tolerability.Expert opinion on drug safety · 2022Review
- Safety, effectiveness and tolerability of sublingual ketamine in depression and anxiety: A retrospective study of off-label, at-home use.Frontiers in psychiatry · 2022Article
- Transcranial magnetic stimulation and intravenous ketamine combination therapy for treatment-resistant bipolar depression: A case report.Frontiers in psychiatry · 2022Article
- Ketamine for Bipolar Depression: Biochemical, Psychotherapeutic, and Psychedelic Approaches.Frontiers in psychiatry · 2022Article
- Retracing our steps to understand ketamine in depression: A focused review of hypothesized mechanisms of action.The mental health clinician · 2021Review
Corrections and comments
PubMed lists nothing against this paper. Absence here is not a guarantee, only a check that was made.
Authors and funding
6 authors at 2 institutions in 1 country.
Funding
No grant is acknowledged in the PubMed record.
Abstract
The rapid antidepressant effect of ketamine has become a breakthrough in the research and treatment of depression. Although predictive and modulating factors of the response to ketamine are broadly studied, little is known about optimal concurrent medication protocols. Concerning gamma-aminobutyric acid neurotransmission being a shared target for both ketamine and benzodiazepines (BZD), we evaluated the influence of BZD on the antidepressant effect of a single ketamine infusion in depressed patients. Data from 47 patients (27 females) with major depression (MADRS ≥ 20, ≥ 1 prior nonresponse to antidepressant treatment in current episode) who participated in two previous studies (EudraCT Number: 2009-010625-39 and 2013-000952-17) entered the analysis. All of the subjects were given an infusion of a subanesthetic dose of racemic ketamine (0.54 mg per kg) as an add-on medication to ongoing antidepressant treatment. Thirteen patients (28%) reached ≥ 50% reduction in MADRS within one week after ketamine administration. Nineteen (40%) patients took concomitant benzodiazepines on a daily basis. The doses of BZDs were significantly higher in nonresponders (p=0.007). ROC analysis distinguished responders from nonresponders by a criterion of >8mg of diazepam equivalent dose (DZ equivalent) with a sensitivity of 80% and a specificity of 85% (p<0.001). RM-ANOVA revealed a different time pattern of response to ketamine between the BZD+ (>8mg of DZ equivalent) and BZD- (≤8mg of DZ equivalent) groups, with a significantly worse outcome in BZD+ on day 3 (p=0.04) and day 7 (p=0.02). The results of the study indicate that concomitant benzodiazepine treatment in higher doses may attenuate ketamine's antidepressant effect. The pathophysiological, clinical and methodological implications of this finding should be considered in future research and ketamine treatment.
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Registered trials
Read under generation 80e0d062 · epoch 390. Bibliography from PubMed, PubMed Central and OpenAlex; grants from NIH RePORTER; trial links from ClinicalTrials.gov; estimates, votes and beliefs from the OpenQuestion graph.